Controlled release of all- trans -retinoic acid from PEGylated gelatin nanopaticles by enzymatic degradation

A new targeting drug carrier for anticancer drug, all- trans -retinoic acid (atRA), was proposed by using angiogenesis which is one of the specific physiological properties of cancer cells. The proposed drug carrier was prepared as PEGylated gelatin nanoparticle (176 nm size). The gelatin molecules were aggregated by coupled deoxycholic acid and the surface of the nanoparticles was covered by polyethylene glycol to reduce reticuloendothelial system (RES) uptake. To prove the feasibility of the nanoparticles as a targeting drug carrier, the degradation of the nanoparicles by collagenase IV and the release pattern of atRA from the nanoparticles by enzymatic degradation were evaluated. The PEGylated gelatin nanoparticles were significantly degraded by collagenase IV within 10 seconds, with most of them degraded within 1 min. When atRA loaded in the PEGylated gelatin nanoparticles was released in phosphate buffered saline (PBS), only twelve percent of atRA were released for one hour. However, when the nanoparticles were put into PBS with collagenase IV of 0.1 μM, a burst effect of atRA was about 40% for the initial 10 min, followed by a continuous release of atRA upto 75% for 5 hr. Therefore, the PEGylated gelatin nanoparticles released anticancer drug very sensitively by collagenase IV, which is one of major matrix metalloproteases involved in angiogenesis. These results showed a feasibility that PEGylated gelatin nanoparticles could be used as a new targeting anticancer drug carrier using angiogenesis as a specific physiological property of cancer cells.